BASIC PHARMACOLOGY FOR CARDIOVASCULAR SYSTEM

PHARMACOLOGY
CARDIOVASCULAR SYSTEM
JHONEE BALMEO R.N.
PHARMACOLOGY (NCM 106) INSTRUCTOR

PREVENTION OF ATHEROMA:
LOWERING PLASMA CHOLESTEROL AND
OTHER APPROACHES
• ATHEROMA IS THE MOST COMMON CAUSE OF ISCHAEMIC HEART
DISEASE, STROKE AND PERIPHERAL VASCULAR DISEASE. SINCE
THESE ARE THE MAJOR CAUSES OF MORBIDITY AND MORTALITY
AMONG ADULTS IN INDUSTRIALIZED SOCIETIES, ITS PREVENTION IS
OF GREAT IMPORTANCE.

LOWERING PLASMA CHOLESTEROL AND
OTHER APPROACHES
• ATHEROMATOUS PLAQUES ARE
FOCAL LESIONS OF LARGE-
AND MEDIUM SIZED ARTERIES
(FIGURE 27.1). THEY START AS
FATTY STREAKS IN THE INTIMA
AND PROGRESS TO
PROLIFERATIVE FIBRO-FATTY
GROWTHS THAT CAN
PROTRUDE INTO THE
VASCULAR LUMEN AND LIMIT

• PREVENTION OF ATHEROMA
MODIFIABLE RISK FACTORS ARE POTENTIALLY SUSCEPTIBLE TO
THERAPEUTIC INTERVENTION. THESE INCLUDE SMOKING, OBESITY,
SEDENTARY HABITS, DYSLIPIDAEMIA, GLUCOSE INTOLERANCE AND
HYPERTENSION.

DRUGS USED TO TREAT DYSLIPIDAEMIA
• THE THREE MAIN CLASSES OF DRUGS USED TO TREAT
DYSLIPIDAEMIA ARE:
THE STATINS (HMG COA REDUCTASE INHIBITORS), DRUGS THAT
BLOCK CHOLESTEROL ABSORPTION AND FIBRATES .

• STATINS
• USE
SIMVASTATIN, PRAVASTATIN, ATORVASTATIN AND ROSUVASTATIN
ARE AVAILABLE IN THE PHILIPPINES. RANDOMIZED CONTROLLED
TRIALS HAVE SHOWN THAT SIMVASTATIN, ATORVASTATIN AND
PRAVASTATIN REDUCE CARDIAC EVENTS AND PROLONG LIFE, AND
ARE SAFE.

• MECHANISM OF ACTION
STATINS INHIBIT THIS ENZYME, LOWERING CYTOPLASMIC
CHOLESTEROL. HEPATOCYTES RESPOND BY INCREASING THE
SYNTHESIS OF LDL RECEPTORS. THIS INCREASES HEPATIC LDL
UPTAKE FROM THE PLASMA, FURTHER REDUCING THE PLASMA LDL
CONCENTRATION.

ADVERSE EFFECTS AND CONTRAINDICATIONS
MILD AND INFREQUENT SIDE EFFECTS INCLUDE,
• NAUSEA, CONSTIPATION, DIARRHOEA, FLATULENCE,
• FATIGUE, INSOMNIA AND RASH.
• MORE SERIOUS ADVERSE EVENTS ARE RARE, BUT INCLUDE
HEPATITIS AND ANGIOEDEMA.

• LIVER FUNCTION TESTS SHOULD BE PERFORMED BEFORE STARTING
TREATMENT AND AT INTERVALS THEREAFTER, AND PATIENTS
SHOULD BE WARNED TO STOP THE DRUG AND REPORT AT ONCE
FOR DETERMINATION OF CREATINE KINASE IF THEY DEVELOP
MUSCLE ACHES.
• SHOULD BE AVOIDED IN ALCOHOLICS AND PATIENTS WITH ACTIVE
LIVER DISEASE, AND ARE CONTRAINDICATED DURING PREGNANCY.

DRUGS THAT REDUCE CHOLESTEROL
ABSORPTION
EZETIMIBE
• USE
• EZETIMIBE IS MOST OFTEN USED IN COMBINATION WITH DIET AND
STATINS FOR SEVERE HYPERCHOLESTEROLAEMIA; ALSO IN
OCCASIONAL PATIENTS WHO CANNOT TOLERATE STATINS OR
WHERE STATINS ARE CONTRAINDICATED.
• EXAMPLE: EZETROL

ABSORPTION
MECHANISM OF ACTION
• IT BLOCKS THE STEROL TRANSPORTER IN THE BRUSH BORDER OF
ENTEROCYTES, PREVENTING CHOLESTEROL AND PLANT STEROLS
(PHYTOSTEROLS) TRANSPORT FROM THE INTESTINAL LUMEN. THIS
MECHANISM IS DISTINCT FROM THAT OF PHYTOSTEROL AND
PHYTOSTANOL ESTERS (PRESENT IN ‘HEALTH’ FOODS SUCH AS
BENECOL™) WHICH INTERFERE WITH THE MICELLAR PRESENTATION
OF STEROLS TO THE CELL SURFACE, OR OF RESINS WHICH BIND
BILE ACIDS IN THE GUT LUMEN.

ABSORPTION
• PHARMACOKINETICS
• EZETIMIBE IS ADMINISTERED BY MOUTH AND IS ABSORBED INTO
INTESTINAL EPITHELIAL CELLS, WHERE IT LOCALIZES TO THE BRUSH
BORDER. IT IS METABOLIZED, FOLLOWED BY ENTEROHEPATIC
RECYCLING AND SLOW ELIMINATION.
• IT ENTERS BREAST MILK.

ABSORPTION
• DIARRHOEA, ABDOMINAL PAIN
• HEADACHES ARE OCCASIONAL PROBLEMS;
• RASH
• ANGIOEDEMA HAVE BEEN REPORTED.
• IT IS CONTRAINDICATED IN BREAST-FEEDING.

ABSORPTION
FIBRATES
• USE
BEZAFIBRATE, GEMFIBROZIL AND FENOFIBRATE ARE AVAILABLE IN
THE PHILIPPINES AND ARE USED MAINLY FOR PATIENTS WITH MIXED
DYSLIPIDAEMIA WITH SEVERELY RAISED TRIGLYCERIDES ESPECIALLY
IF THEY ARE POORLY RESPONSIVE TO STATINS.

ABSORPTION
MECHANISM OF ACTION
• FIBRATES ARE AGONISTS AT A NUCLEAR RECEPTOR WHICH IS
PRESENT IN MANY TISSUES INCLUDING FAT. THE ENSUING EFFECTS
ARE INCOMPLETELY UNDERSTOOD.
• THEY STIMULATE LIPOPROTEIN LIPASE AND INCREASE LDL UPTAKE
BY THE LIVER. IN ADDITION TO THEIR EFFECTS ON PLASMA LIPIDS,
FIBRATES LOWER FIBRINOGEN.

ABSORPTION
ADVERSE EFFECTS
• FIBRATES CAN CAUSE MYOSITIS (IN SEVERE CASES
RHABDOMYOLYSIS WITH ACUTE RENAL FAILURE), ESPECIALLY IN
ALCOHOLICS (IN WHOM THEY SHOULD NOT BE USED) AND IN
PATIENTS WITH IMPAIRED RENAL FUNCTION.
• THE RISK OF MUSCLE DAMAGE IS INCREASED IF THEY ARE TAKEN
WITH A STATIN, ALTHOUGH LIPID SPECIALISTS SOMETIMES EMPLOY
THIS COMBINATION. THEY CAN CAUSE A VARIETY OF
GASTROINTESTINAL SIDE EFFECTS, BUT ARE USUALLY WELL

ABSORPTION
CONTRAINDICATIONS
• FIBRATES SHOULD BE USED WITH CAUTION, IF AT ALL, IN PATIENTS
WITH RENAL OR HEPATIC IMPAIRMENT.
• THEY SHOULD NOT BE USED IN PATIENTS WITH GALL-BLADDER
DISEASE OR WITH HYPOALBUMINAEMIA.
• THEY ARE CONTRAINDICATED IN PREGNANCY AND IN ALCOHOLICS

HYPERTENSION
• SYSTEMIC ARTERIAL HYPERTENSION IS ONE OF THE STRONGEST
KNOWN MODIFIABLE RISK FACTORS FOR ISCHAEMIC HEART
DISEASE, STROKE, RENAL FAILURE AND HEART FAILURE.
• IT REMAINS POORLY TREATED. AS AN ASYMPTOMATIC DISORDER,
PEOPLE ARE UNDERSTANDABLY RELUCTANT TO ACCEPT ADVERSE
DRUG EFFECTS IN ADDITION TO THE INCONVENIENCE OF LONG-
TERM TREATMENT. IN THIS REGARD, MODERN DRUGS REPRESENT
AN ENORMOUS IMPROVEMENT.

HYPERTENSION
• THE KIDNEY PLAYS A KEY ROLE IN THE CONTROL OF BLOOD
PRESSURE AND IN THE PATHOGENESIS OF HYPERTENSION.
SECRETION OF RENIN INFLUENCES VASCULAR TONE AND
ELECTROLYTE BALANCE VIA ACTIVATION OF THE RENIN–
ANGIOTENSIN–ALDOSTERONE SYSTEM.

HYPERTENSION
• ANTIHYPERTENSIVE
AGENTS: ARE INITIATED
WHEN DIASTOLIC BLOOD
PRESSURE IS HIGHER THAT
90MM/HG.

HYPERTENSION
• CARDIOVASCULAR DRUGS WORK BY AUGMENTING OR INHIBITING
THESE PROCESSES. THE MAIN SUCH DRUGS FOR TREATING
HYPERTENSION CAN USEFULLY BE GROUPED AS:
• A. ANGIOTENSIN-CONVERTING ENZYME INHIBITORS (ACEI) AND
ANGIOTENSIN AT1 RECEPTOR ANTAGONISTS;
• B. BETA-ADRENOCEPTOR ANTAGONISTS;
• C. CALCIUM CHANNEL ANTAGONISTS;
• D. DIURETICS.

GENERAL PRINCIPLES OF MANAGING
ESSENTIAL HYPERTENSION
• CONSIDER BLOOD PRESSURE IN THE CONTEXT OF OTHER RISK
FACTORS: USE CARDIOVASCULAR RISK TO MAKE DECISIONS ABOUT
WHETHER TO START DRUG TREATMENT AND WHAT TARGET TO
AIM FOR.
• USE NON-DRUG MEASURES (E.G. SALT RESTRICTION) IN ADDITION
TO DRUGS
• EXPLAIN GOALS OF TREATMENT AND AGREE A PLAN THE PATIENT

• REVIEW THE POSSIBILITY OF CO-EXISTING DISEASE (E.G. GOUT,
ANGINA) THAT WOULD INFLUENCE THE CHOICE OF DRUG.
• THE ‘ABCD’ RULE PROVIDES A USEFUL BASIS FOR STARTING DRUG
TREATMENT.
• USE A LOW DOSE AND, EXCEPT IN EMERGENCY SITUATIONS,
TITRATE THIS UPWARD GRADUALLY.
• ADDITION OF A SECOND DRUG IS OFTEN NEEDED. IT IS BETTER TO
USE SUCH COMBINATIONS THAN TO USE VERY HIGH DOSES OF
SINGLE DRUGS: THIS SELDOM WORKS AND OFTEN CAUSES

• LOSS OF CONTROL – IF BLOOD PRESSURE CONTROL, HAVING BEEN
WELL ESTABLISHED, IS LOST, THERE ARE SEVERAL POSSIBILITIES TO
BE CONSIDERED:
• • NON-ADHERENCE;
• • DRUG INTERACTION – E.G. WITH NON-STEROIDAL
ANTIINFLAMMATORY DRUGS (NSAIDS)
• • INTERCURRENT DISEASE – E.G. RENAL IMPAIRMENT,
ATHEROMATOUS RENAL ARTERY STENOSIS.

DRUGS USED TO TREAT HYPERTENSION
(A DRUGS)
ANGIOTENSIN-CONVERTING ENZYME INHIBITORS
• USE
• SEVERAL ANGIOTENSIN-CONVERTING ENZYME INHIBITORS (ACEI) ARE IN
CLINICAL USE (E.G. RAMIPRIL, TRANDOLAPRIL, ENALAPRIL, LISINOPRIL,
CAPTOPRIL). THESE DIFFER IN THEIR DURATION OF ACTION. LONGER-
ACTING DRUGS (E.G. TRANDOLAPRIL, RAMIPRIL) ARE PREFERRED.
• THEY ARE GIVEN ONCE DAILY AND PRODUCE GOOD 24-HOUR CONTROL.

(A DRUGS)
CAPTOPRIL:
• TRADE NAME: CAPOTIN, INHABACE.
• CLASS: ANTIHYPERTENSIVE, INHIBITOR OF ANGIOTENSIN
SYNTHESIS.
• DOSAGE:
• TABLETS: - 12.5 MG 2-3 TIME PER DAY. –
• IF THERE IS NO RESPONSE, AFTER 1-2 WEEKS, INCREASE
DOSE TO 25 MG 2-3 TIME PER DAY

(A DRUGS)
ENALAPRIL MALEATE
• CLASS: ACE-INHIBITOR
• USES: HYPERTENSION
• DOSE: INITIALLY, 5 MG P.O. ONCE DAILY; THEN ADJUSTED BASED
ON RESPONSE. USUAL DOSAGE RANGE IS 10 TO 40 MG DAILY AS A
SINGLE DOSE OR TWO DIVIDED DOSES. OR, 1.25 MG I.V. INFUSION
OVER 5 MINUTES Q 6 HOURS.
• ADJUST-A-DOSE: IF PATIENT IS TAKING DIURETICS OR CREATININE
CLEARANCE IS 30 ML/MINUTE OR LESS, INITIALLY, 2.5 MG P.O.

(A DRUGS)
• SIMILARLY AN ACEI OR SARTAN IS PREFERRED OVER OTHER ANTI-
HYPERTENSIVES IN DIABETIC PATIENTS BECAUSE THEY SLOW THE
PROGRESSION OF DIABETIC NEPHROPATHY.
• TREATMENT IS INITIATED USING A SMALL DOSE GIVEN LAST THING AT
NIGHT. IF POSSIBLE, DIURETICS SHOULD BE WITHHELD FOR ONE OR TWO
DAYS BEFORE THE FIRST DOSE.
• THE DOSE IS SUBSEQUENTLY USUALLY GIVEN IN THE MORNING AND
INCREASED GRADUALLY IF NECESSARY, WHILE MONITORING THE BLOOD-
PRESSURE RESPONSE.

(A DRUGS)
MECHANISM OF ACTION
• ACE CATALYSES THE CLEAVAGE OF A PAIR OF AMINO ACIDS FROM
SHORT PEPTIDES, THEREBY ‘CONVERTING’ THE INACTIVE DECAPEPTIDE
ANGIOTENSIN I TO THE POTENT VASOCONSTRICTOR ANGIOTENSIN II. AS
WELL AS ACTIVATING THE VASOCONSTRICTOR ANGIOTENSIN IN THIS
WAY, IT ALSO INACTIVATES BRADYKININ – A VASODILATOR PEPTIDE.
• ACEI LOWER BLOOD PRESSURE BY REDUCING ANGIOTENSIN II AND
PERHAPS ALSO BY INCREASING VASODILATOR PEPTIDES, SUCH AS
BRADYKININ. ANGIOTENSIN II CAUSES ALDOSTERONE SECRETION,
INHIBITION OF THIS CONTRIBUTES TO THE ANTIHYPERTENSIVE EFFECT

• THE ENZYME IS RESPONSIBLE
FOR THE CONVERSION OF
ANGIOTENSIN I TO
ANGIOTENSIN II WHICH
DECREASE BP.
• DECREASE ALDOSTERONE
SECRETION WHICH WORKS TO
INCREASE LEVEL OF SERUM
POTASSIUM.

(A DRUGS)
ADVERSE EFFECTS
ACE INHIBITORS ARE GENERALLY WELL TOLERATED. ADVERSE
EFFECTS INCLUDE:
• FIRST-DOSE HYPOTENSION.
• DRY COUGH – THIS IS THE MOST FREQUENT SYMPTOM (5–30% OF
CASES) DURING CHRONIC DOSING. IT IS OFTEN MILD, BUT CAN BE
TROUBLESOME. THE CAUSE IS UNKNOWN, BUT IT MAY BE DUE TO
KININ ACCUMULATION STIMULATING COUGH AFFERENTS.

(A DRUGS)
ADVERSE EFFECTS
• FUNCTIONAL RENAL FAILURE – THIS OCCURS PREDICTABLY IN
PATIENTS WITH HAEMODYNAMICALLY SIGNIFICANT BILATERAL
RENAL ARTERY STENOSIS, AND IN PATIENTS WITH RENAL ARTERY
STENOSIS IN THE VESSEL SUPPLYING A SINGLE FUNCTIONAL
KIDNEY.
• HYPERKALAEMIA IS POTENTIALLY HAZARDOUS IN PATIENTS WITH
RENAL IMPAIRMENT AND GREAT CAUTION MUST BE EXERCISED IN
THIS SETTING. THIS IS EVEN MORE IMPORTANT WHEN SUCH

(A DRUGS)
ADVERSE EFFECTS
• FETAL INJURY – ACEI CAUSE RENAL AGENESIS/FAILURE IN THE
FETUS, RESULTING IN OLIGOHYDRAMNIOS. ACEI ARE THEREFORE
CONTRAINDICATED IN PREGNANCY.
• SULPHHYDRYL GROUP-RELATED EFFECTS – HIGH-DOSE CAPTOPRIL
CAUSES HEAVY PROTEINURIA, NEUTROPENIA, RASH AND TASTE
DISTURBANCE, ATTRIBUTABLE TO ITS SULPHHYDRYL GROUP.

(A DRUGS)
PHARMACOKINETICS
• CURRENTLY AVAILABLE ACE INHIBITORS ARE ALL ACTIVE WHEN
ADMINISTERED ORALLY, BUT ARE HIGHLY POLAR AND ARE
ELIMINATED IN THE URINE.
• A NUMBER OF THESE DRUGS (E.G. CAPTOPRIL, LISINOPRIL) ARE
ACTIVE PER SE, WHILE OTHERS (E.G. ENALAPRIL) ARE PRODRUGS
AND REQUIRE METABOLIC CONVERSION TO ACTIVE METABOLITES
(E.G. ENALAPRILAT). IN PRACTICE, THIS IS OF LITTLE OR NO
IMPORTANCE.

(A DRUGS)
DRUG INTERACTIONS
• THE USEFUL INTERACTION WITH DIURETICS HAS ALREADY BEEN
ALLUDED TO ABOVE. DIURETIC TREATMENT INCREASES PLASMA RENIN
ACTIVITY AND THE CONSEQUENT ACTIVATION OF ANGIOTENSIN II AND
ALDOSTERONE LIMITS THEIR EFFICACY.
• ACE INHIBITION INTERRUPTS THIS LOOP AND THUS ENHANCES THE
HYPOTENSIVE EFFICACY OF DIURETICS, AS WELL AS REDUCING
THIAZIDE-INDUCED HYPOKALAEMIA. AS WITH OTHER
ANTIHYPERTENSIVE DRUGS, NSAIDS INCREASE BLOOD PRESSURE IN

(A DRUGS)
ANGIOTENSIN RECEPTOR BLOCKERS
• SEVERAL ANGIOTENSIN RECEPTOR BLOCKERS (ARB OR ‘SARTANS’)
ARE IN CLINICAL USE (E.G.
LOSARTAN,CANDESARTAN,IRBESARTAN,VALSARTAN).

(A DRUGS)
USE
• SARTANS ARE PHARMACOLOGICALLY DISTINCT FROM ACEI, BUT
CLINICALLY SIMILAR IN HYPOTENSIVE EFFICACY. HOWEVER, THEY
LACK THE COMMON ACEI ADVERSE EFFECT OF DRY COUGH.
• LONG-ACTING DRUGS (E.G. CANDESARTAN, WHICH FORMS A
STABLE COMPLEX WITH THE AT1 RECEPTOR) PRODUCE GOOD 24-
HOUR CONTROL.

(A DRUGS)
USE
• SIMILARLY, AN ACEI OR A SARTAN IS PREFERRED OVER OTHER ANTI-
HYPERTENSIVE DRUGS IN DIABETIC PATIENTS WHERE THEY SLOW THE
PROGRESSION OF NEPHROPATHY.
• HEAD TO HEAD COMPARISON OF LOSARTAN VERSUS ATENOLOL IN
HYPERTENSION (THE LIFE STUDY) FAVOURED THE SARTAN.
• FIRST-DOSE HYPOTENSION CAN OCCUR AND IT IS SENSIBLE TO APPLY
SIMILAR PRECAUTIONS AS WHEN STARTING AN ACEI

(A DRUGS)
PHARMACOKINETICS
• SARTANS ARE WELL ABSORBED AFTER ORAL ADMINISTRATION.
• LOSARTAN HAS AN ACTIVE METABOLITE. HALF-LIVES OF MOST
MARKETED ARB ARE LONG ENOUGH TO PERMIT ONCE DAILY
DOSING.

(B DRUGS)
B-ADRENOCEPTOR ANTAGONISTS
USE
• EXAMPLES OF Β-ADRENOCEPTOR ANTAGONISTS CURRENTLY IN
CLINICAL USE ARE PROPRANOLOL, ATENOLOL, METOPROLOL,
ESMOLOL, SOTALOL, LABETOLOL, OXPRENOLOL.
• BETA-BLOCKERS LOWER BLOOD PRESSURE AND REDUCE THE RISK
OF STROKE IN PATIENTS WITH MILD ESSENTIAL HYPERTENSION,
BUT IN SEVERAL RANDOMIZED CONTROLLED

(B DRUGS)
USES:
• 1. HYPERTENSION,
• 2. ANGINAL PECTORIS.
• 3. CARDIAC ARRHYTHMIAS.
• 4. MYOCARDIAL INFARCTION.
• 5. PROPHYLAXIS OF MIGRAINE.

(B DRUGS)
CLASSIFICATION OF Β-ADRENOCEPTOR ANTAGONISTS
• Β-ADRENOCEPTORS ARE SUBDIVIDED INTO Β1-RECEPTORS
(HEART), Β2-RECEPTORS (BLOOD VESSELS, BRONCHIOLES) AND Β3-
RECEPTORS (SOME METABOLIC EFFECTS, E.G. IN BROWN FAT).
• CARDIOSELECTIVE DRUGS (E.G. ATENOLOL, METOPROLOL,
BISOPROLOL, NEBIVOLOL) INHIBIT Β1-RECEPTORS WITH LESS
EFFECT ON BRONCHIAL AND VASCULAR Β2-RECEPTORS. HOWEVER,
EVEN CARDIOSELECTIVE DRUGS ARE HAZARDOUS FOR PATIENTS

(B DRUGS)
MECHANISM OF ACTION
• Β-ADRENOCEPTOR ANTAGONISTS REDUCE CARDIAC OUTPUT (VIA
NEGATIVE CHRONOTROPIC AND NEGATIVE INOTROPIC EFFECTS ON
THE HEART), INHIBIT RENIN SECRETION AND SOME HAVE
ADDITIONAL CENTRAL ACTIONS REDUCING SYMPATHETIC
OUTFLOW FROM THE CENTRAL NERVOUS SYSTEM (CNS).

(B DRUGS)
CONTRAINDICATIONS:
• BRADYCARDIA, C.H.F., CARDIOGENIC SHOCK, DIABETES,
THYROTOXICOSIS, CHRONIC BRONCHITIS, ASTHMA,
BRONCHOSPASM, EMPHYSEMA.
SIDE EFFECTS:
• BRADYCARDIA, C.H.F., HYPOTENSION, COLD EXTREMITIES (DUE TO
PERIPHERAL VASOCONSTRICTION), EDEMA, DYSPNIA, SHORTNESS
OF BREATH, NAUSEA, VOMITING, HEPATOMEGALY AND

(B DRUGS)
TREATING OVERDOSE:
• 1. INDUCING VOMITING, GASTRIC LAVAGE.
• 2. ARTIFICIAL RESPIRATION.
• 3. GIVE ATROPINE SULFATE 0.6 MG (UP TO 3 MG) AND GLYCOGAN
FOR THE TREATMENT OF BRADYCARDIA.
• 4. TREAT HYPOGLYCEMIA AND HYPOKALEMIA.
• 5. I.V FLUIDS.
• 6. ADRENALINE OR DOPAMINE TO INCREASE BLOOD PRESSURE.

(B DRUGS)
ATENOLOL:
• TRADE NAME: NORMATIN.
• CLASSIFICATION: BETA-ADRENERGIC BLOCKING AGENT CLASSIFICATION:
BETA 1 –ADRENORECEPTR BLOCKING DRUG WHICH IS A CARDIOSELECTIVE.
• USES: HYPERTENSION ANGINA PECTORIS.
• DOSAGE:
• TABLETS: 50 MG OR 100 MG DAILY INITIAL DOSE IS 50 MG, IF THERE IS
NO RESPONSE, INCREASE DOSE TO 100 MG DAILY. IV IN CASE OF ACUTE
MI: GIVE 5 MG OVER 5 MINUTES, AND IF THERE IS NO RESPONSE, GIVE

(B DRUGS)
PROPRANOLOL HYDROCHLORIDE
• TRADE NAME: INDERAL, DERALIN
• CLASSIFICATION: BETA-ADRENERGIC BLACKING AGENT, ANTIARRYHTHMIC.
ACTION: MANIFESTS BOTH BETA1 AND BETA 2 ADRENERGIC BLOCKING
ACTIVITY.
• INDICATION: 1. ANGINA PECTORIS. 2. HYPERTENSION. 3. CARDIAC
ARRHYTMIAS. 4. PROPHYLAXIS OF MIGRIN. 5. PROPHYLAXIS OF MI. 6.
PHEOCHROMOCYTOMA

(C DRUGS)
CALCIUM-CHANNEL BLOCKERS
• DRUGS THAT BLOCK VOLTAGE-DEPENDENT CA2+ CHANNELS ARE
USED TO TREAT ANGINA AND SUPRAVENTRICULAR
TACHYDYSRHYTHMIAS, AS WELL AS HYPERTENSION.
• THERE ARE THREE CLASSES: DIHYDROPYRIDINES,
BENZOTHIAZEPINES AND PHENYLALKYLAMINES.

(C DRUGS)
USE
• DIHYDROPYRIDINE CALCIUM-CHANNEL BLOCKERS. AMLODIPINE HAS BEEN
COMPARED DIRECTLY WITH A DIURETIC (CHLORTALIDONE) AND AN ACEI
(LISINOPRIL).
• IT IS A GOOD CHOICE, ESPECIALLY IN OLDER PATIENTS, ALTHOUGH MORE
EXPENSIVE THAN CHLORTALIDONE.
• AMLODIPINE IS TAKEN ONCE DAILY. THE DAILY DOSE CAN BE INCREASED
IF NEEDED USUALLY AFTER A MONTH OR MORE.

(C DRUGS)
MECHANISM OF ACTION
• CALCIUM-CHANNEL BLOCKERS INHIBIT CA2+ INFLUX THROUGH
VOLTAGE-DEPENDENT L-TYPE CALCIUM CHANNELS. CYTOPLASMIC
CA2+ CONCENTRATIONS CONTROL THE CONTRACTILE STATE OF
ACTOMYOSIN.
• CALCIUM-CHANNEL BLOCKERS THEREFORE RELAX ARTERIOLAR
SMOOTH MUSCLE, REDUCE PERIPHERAL VASCULAR RESISTANCE
AND LOWER ARTERIAL BLOOD PRESSURE.

(C DRUGS)
ADVERSE EFFECTS
CALCIUM-CHANNEL BLOCKING DRUGS ARE USUALLY WELL
TOLERATED.
• • SHORT-ACTING PREPARATIONS (E.G. NIFEDIPINE CAPSULES)
CAUSE FLUSHING AND HEADACHE.
• • ANKLE SWELLING (OEDEMA) IS COMMON, OFTEN TROUBLESOME,
BUT NOT SINISTER.
• • CONSTIPATION IS COMMON WITH VERAPAMIL.

(C DRUGS)
PHARMACOKINETICS
• CALCIUM-CHANNEL ANTAGONISTS ARE ABSORBED WHEN GIVEN BY
MOUTH. NIFEDIPINE HAS A SHORT HALF-LIFE AND MANY OF ITS
ADVERSE EFFECTS RELATE TO THE PEAK PLASMA CONCENTRATION.
• SLOW-RELEASE PREPARATIONS IMPROVE ITS PROFILE IN THIS REGARD.
AMLODIPINE IS RENALLY ELIMINATED AND HAS A HALF-LIFE OF TWO
TO THREE DAYS AND PRODUCES A PERSISTENT ANTIHYPERTENSIVE
EFFECT WITH ONCE DAILY ADMINISTRATION.

(D DRUGS)
DIURETICS
THE KIDNEY IS A COMPLEX ORGAN WITH 3 MAIN FUNCTIONS:
1- MAINTAIN THE ACID-BASE BALANCE.
2- ELIMINATION OF WASTE MATERIALS & RETURN OF USEFUL
METABOLITES TO THE BLOOD.
3- MAINTENANCE OF AN ADEQUATE ELECTROLYTE BALANCE WHICH
IN TURN GOVERNS THE AMOUNT OF FLUID RETAINED IN THE BODY.

(D DRUGS)
ACTION OF DIURETICS:
• IT INCREASE THE URINARY OUTPUT OF WATER AND SODIUM “ PREVENTION
OR CORRECTION OF EDEMA” THROUGH ONE OF THE FOLLOWING
MECHANISMS:
• 1- INCREASING THE GLOMERULAR FILTRATION RATE .
• 2- DECREASING THE RATE AT WHICH SODIUM IS REABSORBED FROM THE
GLOMERULAR FILTRATE BY THE RENAL TUBULES, THEREFORE WATER IS
EXCRETED ALONG WITH SODIUM .
• 3- PROMOTING THE EXCRETION OF SODIUM & THEREFORE WATER BY THE

(D DRUGS)
ADVERSE EFFECTS
• METABOLIC AND ELECTROLYTE CHANGES INVOLVE:
• HYPONATRAEMIA – SOMETIMES SEVERE, ESPECIALLY IN THE
ELDERLY;
• HYPOKALAEMIA –MILD HYPOKALAEMIA IS COMMON BUT SELDOM
CLINICALLY IMPORTANT IN UNCOMPLICATED HYPERTENSION;
• HYPOMAGNESAEMIA;
• HYPERURICAEMIA – MOST DIURETICS REDUCE URATE CLEARANCE,
INCREASE PLASMA URATE AND CAN PRECIPITATE GOUT;

(D DRUGS)
• ADVERSE EFFECTS
• HYPERGLYCAEMIA – THIAZIDES REDUCE GLUCOSE TOLERANCE:
HIGH DOSES CAUSE HYPERGLYCAEMIA IN TYPE 2 DIABETES;
• HYPERCALCAEMIA – THIAZIDES REDUCE URINARY CALCIUM ION
CLEARANCE (UNLIKE LOOP DIURETICS, WHICH INCREASE IT) AND
CAN AGGRAVATE HYPERCALCAEMIA IN HYPERTENSIVE PATIENTS
WITH HYPERPARATHYROIDISM;
• HYPERCHOLESTEROLAEMIA – HIGH-DOSE THIAZIDES CAUSE A
SMALL INCREASE IN PLASMA LDLCHOLESTEROL CONCENTRATION.

(D DRUGS)
ADVERSE EFFECTS
• ERECTILE DYSFUNCTION WHICH IS REVERSIBLE ON STOPPING THE
DRUG.
• INCREASED PLASMA RENIN, LIMITING THE ANTIHYPERTENSIVE
EFFECT.
• IDIOSYNCRATIC REACTIONS, INCLUDING RASHES (WHICH MAY BE
PHOTOSENSITIVE) AND PURPURA, WHICH MAY BE
THROMBOCYTOPENIC OR NON-THROMBOCYTOPENIC.

(D DRUGS)
• 1- CARBONIC ANHYDRASE INHIBITOR DIURETICS:
ACETAZOLAMIDE
TRADE NAME : DIAMOX
CLASS. : ANTICONVULSANT, DIURETIC.
AS A DIURETIC: IT INHIBITS CARBONIC ANHYDRASE IN THE
KIDNEYS
*HAS A LIMITED USE AS A DIURETIC BECAUSE IT INCREASES THE

(D DRUGS)
CONTRAINDICATIONS:
- LOW SERUM LEVEL OF SODIUM & POTASSIUM.
- - RENAL & HEPATIC DYSFUNCTION.
- - ADRENAL INSUFFICIENCY .
- - HYPERSENSITIVITY TO THIAZIDE DIURETICS. SIDE EFFECTS:
ANOREXIA, POLYURIA, DROWSINESS, CONFUSION, & ACIDOSIS.
- DOSE: TAB. 4-30 MGKGDAY IN DIVIDED DOSES

(D DRUGS)
• 2- LOOP DIURETICS:
FUROSEMIDE
TRADE NAME : FUSED , LASIX CLASS: LOOP DIURETIC.
ACTION :
- IT INHIBITS THE REABSORPTION OF SODIUM AND CHLORIDE IN THE
ASCENDING LOOP OF HENLE RESULTING IN THE EXCRETION OF SODIUM,
CHLORIDE & TO A LESSER DEGREE POTASSIUM & BICARBONATE IONS. ALSO IT
DECREASE THE REABSORPTION OF SODIUM & CHLORIDE & INCREASE THE
EXCRETION OF POTASSIUM IN THE DISTAL TUBULE.

(D DRUGS)
USES:
- EDEMA ASSOCIATED WITH:
- -CONGESTIVE HEART FAILURE
- -LIVER CIRRHOSIS.
- -NEPHROTIC SYNDROME.
- - ACUTE PULMONARY EDEMA.
- - HYPERTENSION.

(D DRUGS)
• CONTRAINDICATIONS:
- HEPATIC COMA ASSOCIATED WITH ELECTROLYTE DEPLETION.
- - ANURIA
- - SEVER RENAL DISEASES .
- - HYPERSENSITIVITY.

(D DRUGS)
• SIDE EFFECTS:
• - DEHYDRATION, HYPOVLEMIA.
• - HYPOKALEMIA ,HYPERGLYCEMIA, HYPONATREMIA
• - NAUSEA, VOMITING, DIARRHEA, ANOREXIA.
• - TINNITUS, BLURRING OF VISION, HEADACHE, ORTHOSTATIC
HYPOTENSION, RASHES & PHOTOSENSITIVITY.

(D DRUGS)
FORMS: TABLETS 40 MG.
AMPULES 20 MG /2ML , 250 MG /10 ML.
DOSE: ORAL: 20-80 MG AS A SINGLE DOSE.
I.V: 20-40 MG AS A SINGLE DOSE.
FOR HYPERTENSIVE CRISIS:100-200 MG.
*BECAUSE THE DRUG POTENTATES THE EFFECTS OF MUSCLE RELAXANTS,
IT IS RECOMMENDED TO DISCONTINUE ORAL MEDICATION 1 WEEK BEFORE
SURGERY & THE I.V. 2 DAYS BEFORE SURGERY

(D DRUGS)
• 3- OSMOTIC DIURETICS:
MANNITOL
TRADE NAME : OSMITROL
CLASS : OSMOTIC DIURETIC.
ACTION : INCREASE THE OSMOLARITY OF THE GLOMERULAR
FILTRATE WHICH DECREASE THE REABSORPTION OF WATER
WHILE INCREASING THE EXCRETION OF SODIUM AND CHLORIDE

(D DRUGS)
• USES:
• - ACUTE REND FAILURE
• - CEREBRAL EDEMA
• - TO DECREASE INTRACRANIAL PRESSURE
• - GLAUCOMA CONTRAINDICATIONS:
• -ANEMIA
• - DEHYDRATION
• - PULMONARY EDEMA
*PROGRESSIVE HEART FAILURE OR PULMONARY CONGESTION AFTER

(D DRUGS)
• SIDE EFFECTS:
• HYPERNATREMIA , ELECTROLYTE IMBALANCE,
• ACIDOSIS DEHYDRATION, DRY MOUTH , THIRST,
• EDEMA, HYPOTENSION & HYPERTENSION ,
• BLURRING OF VISION , HEADACHE , DIZZINESS.
DOSE: 50 ML OF 25%, 75 ML OF 20 % OR 100 ML OF 15% SOLUTION
INFUSED OVER 3-5 MINUTES.

(D DRUGS)
• 4 . POTASSIUM – SPARING DIURETICS:
SPIRONOLACTONE
TRADE NAME : ALDACTONE.
CLASS: DIURETIC – POTASSIUM SPARING.

(D DRUGS)
ACTION:
- IS A MILD DIURETIC THAT ACTS ON THE DISTAL TUBULE TO
INHIBIT SODIUM EXCHANGE FOR POTASSIUM WHICH RESULTS IN
INCREASED SECRETION OF SODIUM AND WATER &
CONSERVATION OF POTASSIUM .
- IT IS ALSO ALDOSTERONE ANTAGONIST.
- - IT HAS SLIGHT ANTIHYPERTENSIVE EFFECT .

(D DRUGS)
• USES:
- EDEMA DUE TO CONGESTIVE HEART FAILURE
- - LIVER CIRRHOSIS.
- - NEPHROTIC SYNDROME .
- - ESSENTIAL HYPERTENSION.
- - PRIMARY HYPERALDOSTERONISM.
- - HYPOKALEMIA (AS IN CHF).

(D DRUGS)
IT ALSO INTERFERES WITH SYNTHESES OF TESTOSTERONE & MAY
INCREASE FORMATION OF ESTRADIOL FROM TESTOSTERONE THUS
LEADING TO ENDOCRINE ABNORMALITIES.
• CONTTRAINDICATIONS:
- ACUTE RENAL INSUFFICIENCY.
- - PROGRESSIVE RENAL FAILURE.
- PATIENTS RECEIVING POTASSIUM SUPPLEMENT.
- - HYPERKALEMIA

(D DRUGS)
• SIDE EFFECTS:
• - HYPERKALEMIA, HYPONATREMIA ( DRY MOUTH , LETHARGY, THIRST & EASY
FATIGABILITY).
• - VOMITING , DIARRHEA, CRAMPS.
• - MENSTRUAL IRREGULARITIES, GYNECOMASTIA, HIRSUTISM & DEEPING OF
VOICE , IMPOTENCE.
• - SKIS RASHES & BREAST CARCINOMA

(D DRUGS)
5-THIAZIDES & RELATED DIURETICS:
EXAMPLE: HYDROCHLOROTHIAZIDE
TRADE NAME : ESIDREX
• ACTION: PROMOTE DIURESIS BY DECREASING THE RATE AT WHICH
SODIUM & CHLORIDE ARE REABSORBED BY THE DISTAL RENAL
TUBULES OF THE KIDNEY , THUS FORCE EXCRETION OF
ADDITIONAL WATER , ALSO INCREASE THE EXCRETION OF
POTASSIUM & THE EXCRETION OF CALCIUM & URIC ACID .

POTASSIUM CHLORIDE
• TRADE NAME: KCL FOR IV PREPARATION, SLOW K FOR ORAL
PREPARATIONS.
• CLASSIFICATION: ELECTROLYTE, MINERAL.
USES:
• PATIENTS RECEIVING HIGH DOSES OF POTENT DIURETICS.
• PATIENTS HAVING SECONDARY HYPERALDOSTERONISM.
• WHEN THERE IS EXCESSIVE LOSS OF POTASSIUM IN FECES.
• WHEN POTASSIUM INTAKE IS NOT ADEQUATE (ESPECIALLY IN
ELDERLY).

DOSE:
• AVAILABLE IN SLOW RELEASE TABLETS OF 600MG/TABLETS AND IN
AMPULES OF 20 MMOL/10 ML.
• VARY ACCORDING TO PATIENTS' NEEDS
• MAINTENANCE DOSE FOR PATIENTS WHO RECEIVE NORMAL DIET IS
2-4 GM DAILY IN DIVIDED DOSES.
• IV: 20 MMOL IS ADDED TO 500 ML OF IV SOLUTION (D5W OR NS)
AND TO INFUSE SLOWLY OVER 2-3 HOURS.

CONTRAINDICATIONS:
• SEVERE RENAL FAILURE. IF SERUM POTASSIUM LEVEL IS OVER 5
MMOL/LITER.
SIDE EFFECTS:
• HYPERKALEMIA
• PHLEBITIS AT INJECTION SITE.
• HEART TOXICITY IF INFUSED RAPIDLY.
• WITH ORAL TABLET: DYSPEPSIA, NAUSEA AND VOMITING,
ESOPHAGEAL OR BOWEL ULCERATION.

NURSING CONSIDERATIONS:
• MIX SOLUTION WELL.
• ADMINISTER SOLUTION SLOWLY (500 ML OF SOLUTION OVER 2-3
HOURS)
• MONITOR SERUM POTASSIUM LEVEL.
• ASSESS INSERTION SITE FOR SIGNS OF PHLEBITIS.
• GIVE ORAL PREPARATION ON FULL STOMACH.

KEY POINTS
• DIURETICS:
THIAZIDES (IN LOW DOSE) ARE PREFERRED TO LOOP DIURETICS
UNLESS THERE IS RENAL IMPAIRMENT. THEY MAY PRECIPITATE GOUT
AND WORSEN GLUCOSE TOLERANCE OR DYSLIPIDAEMIA, BUT THEY
REDUCE THE RISK OF STROKE AND OTHER VASCULAR EVENTS.
ADVERSE EFFECTS INCLUDE HYPOKALAEMIA, WHICH IS SELDOM
PROBLEMATIC, AND IMPOTENCE. THEY ARE SUITABLE FIRST-LINE
DRUGS, ESPECIALLY IN BLACK PATIENTS, WHO OFTEN HAVE LOW
CIRCULATING RENIN LEVELS AND RESPOND WELL TO SALT
RESTRICTION AND DIURETICS.

KEY POINTS
• BETA-BLOCKERS
REDUCE THE RISK OF VASCULAR EVENTS, BUT ARE
CONTRAINDICATED IN PATIENTS WITH OBSTRUCTIVE PULMONARY
DISEASE. ADVERSE EVENTS (DOSE-RELATED) INCLUDE FATIGUE AND
COLD EXTREMITIES. HEART FAILURE, HEART BLOCK OR
CLAUDICATION CAN BE EXACERBATED IN PREDISPOSED PATIENTS.
THEY ARE PARTICULARLY USEFUL IN PATIENTS WITH ANOTHER
INDICATION FOR THEM (E.G. ANGINA, POSTMYOCARDIAL
INFARCTION). PATIENTS OF AFRICAN DESCENT TEND TO RESPOND
POORLY TO THEM AS SINGLE AGENTS.

KEY POINTS
• ACE INHIBITORS
ARE PARTICULARLY USEFUL AS AN ADDITION TO A THIAZIDE IN
MODERATELY SEVERE DISEASE. THE MAIN ADVERSE EFFECT ON
CHRONIC USE IS COUGH; LOSARTAN, AN ANGIOTENSIN-II RECEPTOR
ANTAGONIST, LACKS THIS EFFECT BUT IS OTHERWISE SIMILAR TO
ACE INHIBITORS.

KEY POINTS
• CALCIUM-CHANNEL ANTAGONISTS
ARE USEFUL, ESPECIALLY IN MODERATELY SEVERE DISEASE. LONG-
ACTING DRUGS/PREPARATIONS ARE PREFERRED. THE MAIN ADVERSE
EFFECT IN CHRONIC USE IS ANKLE SWELLING.
*OTHER DRUGS THAT ARE USEFUL IN OCCASIONAL PATIENTS WITH
SEVERE DISEASE INCLUDE MINOXIDIL, HYDRALAZINE AND
NITROPRUSSIDE.

THANK YOU
ISCHAEMIC HEART DISEASE
ANTICOAGULANTS AND ANTIPLATELET DRUGS
HEART FAILURE
CARDIAC DYSRYTHMIAS
• TO BE DISCUSSED NEXT WEEK

BASIC PHARMACOLOGY FOR CARDIOVASCULAR SYSTEM

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